PD‑1 gene promoter polymorphisms correlate with a poor prognosis in non‑small cell lung cancer

Sasaki,Hidefumi; Tatemaysu,Tsutomu; Okuda,Katsuhiro; Moriyama,Satoru; Yano,Motoki; Fujii,Yoshitaka

doi:10.3892/mco.2014.358

PD‑1 gene promoter polymorphisms correlate with a poor prognosis in non‑small cell lung cancer

Authors:
- Hidefumi Sasaki
- Tsutomu Tatemaysu
- Katsuhiro Okuda
- Satoru Moriyama
- Motoki Yano
- Yoshitaka Fujii
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Affiliations: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan
Published online on: July 24, 2014 https://doi.org/10.3892/mco.2014.358
Pages: 1035-1042

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Abstract

An imbalance to the regulation of the immune system changes the tumor‑specific T‑cell immunity in the cancer microenvironment and adjusts the tumor progression and metastasis. Inhibiting the interactions of the immune function mediates the antitumor activity in preclinical models. The programmed death 1 (PD‑1) gene ‑606 G/A polymorphism, which may modify promoter activity and is Asian‑specific, was investigated by TaqMan quantitative polymerase chain reaction assay in surgically treated non‑small cell lung cancer (NSCLC) cases. In the present study, 583 surgically removed NSCLC cases were included for single‑nucleotide polymorphism (SNP) analyses. The PD‑1 SNP statuses at the promoter region (rs36084323) were 146 AA (25.0%), 293 GA (50.3%) and 144 GG (24.7%). The ratio was extremely similar to the healthy control in a previous study: 24.9% AA, 47.8% GA and 27.3% GG. The ratio of the GG phenotype was not significantly different for gender (25.1% males and 23.9% female), age (25.2% ≤65 years and 24.4% >65 years), smoking status (26.1% smoker and 21.8% non‑smoker) and pathological subtypes [25.4% adenocarcinoma (adeno) and 24.2% squamous cell carcinoma (SCC)]. The GG ratio of PD‑1 was not significantly different between pathological stage II‑IV (25.5%) and stage I cases (24.1%; P=0.6245). The survival time of the patients with the ‑606 GG phenotype of PD‑1 was significantly lower (n=147, 50 succumbed) compared to the patients with ‑606 GA or ‑606 AA (n=435, 109 succumbed) (P=0.0183). The GG phenotype patients had a significantly worse prognosis in the SCC population (P=0.009), however, this was not different to the adeno population (P=0.2594). Thus, PD‑1 may promote tumor prognosis and provide a candidate for the blockade of its function as a strategy to antagonize the progression process in NSCLC, particularly lung SCC.

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